crossing96/oncoscreening huggingface dataset:
Whole-genome and whole-exome sequencing of bladder cancer identifies frequent alterations in genes involved in sister chromatid cohesion and segregation.	Bladder cancer is one of the most common cancers worldwide, with transitional cell carcinoma (TCC) being the predominant form. Here we report a genomic analysis of TCC by both whole-genome and whole-exome sequencing of 99 individuals with TCC. Beyond confirming recurrent mutations in genes previously identified as being mutated in TCC, we identified additional altered genes and pathways that were implicated in TCC. Notably, we discovered frequent alterations in STAG2 and ESPL1, two genes involved in the sister chromatid cohesion and segregation (SCCS) process. Furthermore, we also detected a recurrent fusion involving FGFR3 and TACC3, another component of SCCS, by transcriptome sequencing of 42 DNA-sequenced tumors. Overall, 32 of the 99 tumors (32%) harbored genetic alterations in the SCCS process. Our analysis provides evidence that genetic alterations affecting the SCCS process may be involved in bladder tumorigenesis and identifies a new therapeutic possibility for bladder cancer.	bladder
Recurrent inactivation of STAG2 in bladder cancer is not associated with aneuploidy.	Urothelial bladder cancer (UBC) is heterogeneous at the clinical, pathological and genetic levels. Tumor invasiveness (T) and grade (G) are the main factors associated with outcome and determine patient management. A discovery exome sequencing screen (n = 17), followed by a prevalence screen (n = 60), identified new genes mutated in this tumor coding for proteins involved in chromatin modification (MLL2, ASXL2 and BPTF), cell division (STAG2, SMC1A and SMC1B) and DNA repair (ATM, ERCC2 and FANCA). STAG2, a subunit of cohesin, was significantly and commonly mutated or lost in UBC, mainly in tumors of low stage or grade, and its loss was associated with improved outcome. Loss of expression was often observed in chromosomally stable tumors, and STAG2 knockdown in bladder cancer cells did not increase aneuploidy. STAG2 reintroduction in non-expressing cells led to reduced colony formation. Our findings indicate that STAG2 is a new UBC tumor suppressor acting through mechanisms that are different from its role in preventing aneuploidy.	bladder
Is GATA3 expression maintained in regional metastases?: a study of paired primary and metastatic urothelial carcinomas.	GATA3 has been recognized as a promising marker for primary urothelial carcinoma (UC), consistently showing higher expression levels than urothelial markers thrombomodulin and uroplakin III. However, expression of GATA3 in comparison with UC-associated markers CK7 and p63 has not been systematically studied. Moreover, no studies have been conducted to establish GATA3 sensitivity in regional metastases. In this study, high-density tissue microarrays were constructed from 69 matched paired primary and metastatic bladder tumors including pure urothelial UCs with papillary (n=48) or flat phenotype (n=9), mixed tumors with micropapillary, glandular, small cell, squamous, giant cell, and plasmacytoid features (n=9), and 3 adenocarcinomas. GATA3 was expressed in 62/69 (90%) primary UC and 64/69 (93%) metastases, with significantly higher staining intensity in nodal metastases (P=0.03). In primary tumors, GATA3 was positive in 44/48 (92%) papillary UCs, 9/9 (100%) flat UCs, 8/9 (89%) mixed UCs, and 1/3 (33%) adenocarcinomas, whereas in metastases these numbers were 45/48 (94%), 9/9 (100%), 8/9 (89%), and 2/3 (67%), respectively. The majority of positive cases showed strong diffuse nuclear reactivity: 75% of primary UCs and 79% of metastases. GATA3 sensitivity in primary and metastatic UCs was comparable to that of CK7 and superior to that of p63 (P<0.05). GATA3 specificity was computed in comparison with its morphologic mimics expressing CK7 and p63, including 208 primary and 24 metastatic tumors from the lung, cervix, and head and neck regions. Strong GATA3 expression was present in 2/51 (4%) cervical carcinomas, whereas weak GATA3 expression was present in 7/51 (14%) cervical, 6/74 (8%) head and neck cancers, and 2/83 (3%) lung carcinomas. Remaining 191 primary and 24 metastatic tumors were GATA3 negative. Therefore, specificity of GATA3 calculated on the basis of morphologic and immunophenotypic UC mimics from lung, cervix, head and neck was 92%. Our findings demonstrate high sensitivity and specificity of the GATA3 diagnostic marker, with not only maintained but increased expression in regional metastases.	bladder
[Arterial bypass iterative thrombosis and cancer: three cases].	Cancer associated with venous thromboembolic disease has been recognized since Trousseau, but a link between cancer and iterative arterial thrombosis is rarely described. We report three cases of patients with iterative bypass thrombosis in whom cancer was subsequently diagnosed: lung cancer in one patient and hepatocarcinoma and bladder cancer in the others. Smoking and hypertension were risk factors in both patients. The link between arterial thrombosis and cancer is probably multifactorial. In case of iterative arterial bypass thrombosis, the search for cancer is as useful as the control of cardiovascular risk factors and the search for antiphospholipid syndrome, since patient management can be affected.	bladder
Genito-urological cancers in elderly patients.	"Age is now widely accepted as the greatest single risk factor for developing cancer, and cancer is considered primarily as a disease of the elderly. Furthermore, a characteristic of aging is the progressive deterioration of immune function known as immunosenescence. In addition to the increased risk of occurrence of cancer among older patients, they are more predisposed to poor outcomes after definitive treatment. Therapies, outcomes and mortality are often influenced by age and elderly must have a specific and a multidisciplinary approach. It is obvious to consider that one should not consider ""age"" as the only risk factor, but the condition that this determines to the organism, like the presence of co-morbidities and the consequent poor response to treatment. Cancer occurs frequently in association of one or more other chronic diseases, that affect the efficacy of various treatment interventions. Because of the potential morbidity associated with surgery, the use of mini-invasive techniques have expanded considerably. Aging should not be viewed as a difficulty to definitive therapeutic option. For these reason, it should be correct to value the physiologic capabilities of each organ system and all co-morbidities in the elderly, in order to face possible risks of treatment or improbable benefits. This review takes a look to the tumor biology and to the morbidity of cancer treatment in elderly patients affected by genito-urological cancer like prostate, bladder and renal cancer."	bladder
Prognostic and clinicopathological significance of survivin expression in bladder cancer patients: a meta-analysis.	Survivin has been widely reported to play a role in diagnosis and prognosis of bladder cancer patients. However, published data on this subject are heterogeneous. Here, we conducted a meta-analysis to obtain a complete evaluation of the association between survivin and recurrence-free survival (RFS), disease-specific survival (DSS), overall survival (OS), and odds ratio (OR) in bladder cancer patients. Published studies on this subject were selected for further assessment by online articles in PubMed, MEDLINE, EMBASE, and OVID databases. Pooled hazard ratios (HR) with 95 % confidence interval (95 % CI) were estimated. Funnel plots were used to evaluate the publication bias. As well, heterogeneity and sensitivity were analyzed. In this meta-analysis, we included 13 studies with the total number of 1,963 patients. Positive survivin expression in bladder cancer was associated with a poor RFS (HR, 1.831; 95 % CI, 1.344-2.49), DSS (HR, 1.721; 95 % CI, 1.477-2.004), or OS (HR, 1.753; 95 % CI, 1.092-2.816) in patients. In addition, a significant association between expression of survivin and age (OR, 0.641; 95 % CI, 0.416-0.987) as well as stage (OR, 0.37; 95 % CI, 0.190-0.750) was revealed. Heterogeneity was observed among the included studies with RFS (x (2) =29.58, p = 0.009, I (2) = 52.7 %), OS (x (2) = 15.67, p = 0.008, I (2) = 68.1 %), and stage (x (2) = 11.97, p = 0.035, I (2) = 58.2 %). There was no publication bias according to Begg's and Egger's tests except for studies with gender. Furthermore, sensitivity analysis obtained the source of heterogeneity and confirmed opposite results of some studies. This study suggests that expression of survivin indicates poor prognosis in older patients and muscle invasive or advanced stage in bladder cancer. Survivin expression could be used in identifying a subgroup of patients with potential to benefit from a targeted therapy against survivin.	bladder
Increased SPHK1 expression is associated with poor prognosis in bladder cancer.	Upregulation of sphingosine kinase 1 (SPHK1) protein has been reported to be associated with a poor prognosis in a variety of malignant tumors. However, the role of SPHK1 in bladder cancer (BC) has not been thoroughly elucidated. The purpose of this study was to assess SPHK1 expression and to explore its contribution to BC. Real-time quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) was conducted to detect SPHK1 mRNA expression in 37 pairs of fresh-frozen BC tissues and corresponding noncancerous tissues. Results showed that SPHK1 mRNA expression level in BC tissues was significantly higher than that in corresponding noncancerous tissues. To investigate the association between SPHK1 protein expression and clinicopathological characteristics of BC, immunohistochemistry (IHC) was performed in 153 archived paraffin-embedded BC samples. Interestingly, high SPHK1 expression was significantly associated with histologic grade (P = 0.045) and tumor stage (P < 0.001) of patients with BC. The Kaplan-Meier survival curve showed that patients with high SPHK1 expression had significantly reduced overall 5-year survival rates (P < 0.001). Multivariate Cox regression analysis further suggested that the increased expression of SPHK1 was an independent poor prognostic factor for this disease. In conclusion, our data offer the convincing evidence for the first time that the increased expression of SPHK1 may be involved in the pathogenesis and progression of BC. SPHK1 might be a potential marker to predict the prognosis in BC.	bladder
[Multicentric evaluation of a self-screening questionnaire for occupational bladder cancer].	"OBJECTIVE: Evaluate a self-screening questionnaire for bladder cancer of occupational origin and analyse an influence of exposure to a carcinogen bladder tumor on prognosis. PATIENTS AND METHODS: Five hundred and thirty-one patients followed, between 2005 and 2010, for bladder cancer in two university centers have received a self-screening questionnaire derived from questionnaire KVP 08. Patients who responded positively to at least one of the items were considered to have a self-screening questionnaire ""positive"". Patients were finally invited to take an appointment for consultation in occupational pathology. RESULTS: The response rate to self-screening questionnaire was 39.9% (212/531). It was ""positive"" in 82 cases (38.7%). Among the 82 patients with a self-screening questionnaire ""positive"", 46 patients consulted in occupational pathology (56%). Occupational exposure to a bladder carcinogen was documented in 91.3% of cases. Among the 22 patients who consulted in occupational pathology with a self-screening questionnaire ""negative"", an occupational exposure to a bladder carcinogen was documented in 13.6% of cases. The sensibility of the self-screening questionnaire was 91.3%, the specificity 86.4% and the accuracy 89.7%. The relative risk to have an occupational exposure if the self-screening questionnaire was ""positive"" was 6.69. The analysis of groups ""positive"" versus ""negative"" does not reveal any statistically significant difference in terms of tumor aggressiveness and disease-free survival. CONCLUSION: The self-screening questionnaire was considered relevant with good reliability for detection of occupational exposure to a bladder carcinogen."	bladder
[Surgical treatment of metastatic urothelial carcinoma of the bladder: Review of the Cancer Committee of the French Association of Urology].	INTRODUCTION: The role of surgery in the treatment of patients with metastatic urothelial bladder cancer is controversial. The aim was to review situations where surgical resection of the bladder tumor and/or metastatic urothelial carcinoma has been reported and analyze its results. MATERIALS AND METHODS: A bibliographic research in French and English using the keywords BCG, bladder cancer, metastases, cystectomy, metastasectomy, radiotherapy, curative treatment and palliative treatment was performed, 177 articles have been reviewed, and 18 have been selected. RESULTS: Synchronous or metachronous urothelial carcinoma metastases were diagnosed in 4 and 50% of the cases, respectively. The surgical treatment of metastatic urothelial carcinoma of the bladder has been proposed to achieve oncologic resection of all detectable lesions after a first-line chemotherapy or to treat symptoms, which were refractory to other treatment modalities. In achieving complete resection of the primary tumor and metastases after MVAC chemotherapies, the 5years overall survival was 28%. CONCLUSION: There was no evidence in favouring surgical treatment of metastatic urothelial carcinoma. Considering the high perioperative mortality rate of cystectomy in imperative indications, particularly in the case of hematuria, all therapeutic alternatives must have been exhausted and urine derived in the simplest way.	bladder
Sieve estimation in semiparametric modeling of longitudinal data with informative observation times.	Analyzing irregularly spaced longitudinal data often involves modeling possibly correlated response and observation processes. In this article, we propose a new class of semiparametric mean models that allows for the interaction between the observation history and covariates, leaving patterns of the observation process to be arbitrary. For inference on the regression parameters and the baseline mean function, a spline-based least squares estimation approach is proposed. The consistency, rate of convergence, and asymptotic normality of the proposed estimators are established. Our new approach is different from the usual approaches relying on the model specification of the observation scheme, and it can be easily used for predicting the longitudinal response. Simulation studies demonstrate that the proposed inference procedure performs well and is more robust. The analyses of bladder tumor data and medical cost data are presented to illustrate the proposed method.	bladder
Cyclooxygenase-2 expression in urinary bladder transitional cell carcinoma and its association with clinicopathological characteristics.	BACKGROUND: Transitional cell carcinoma (TCC) is the most predominant type of urinary bladder tumor. As cyclooxygenase (COX)-2 is recently introduced as an attractive target molecule in bladder TCC, we evaluated the immunohistochemical expression of this marker and its association with several clinicopathological characteristics. MATERIALS AND METHODS: This cross-sectional study was performed in the Pathology department of Sina Hospital in Tehran, Iran during 2006-2011. Ninety-two paraffin embedded blocks were selected from patients with urinary bladder TCC who underwent cystectomy or transurethral resection (TUR). Then, we assessed COX-2 expression by immunohistochemical staining using antibody against COX-2. Staining in more than 5% of tumor cells was considered as positive expression. RESULTS: COX-2 was expressed in 50 % of our patients. This marker was markedly expressed in high grade bladder TCC (62.1%) versus other grades and there was statistically a significant difference in COX-2 expression between various grades (p=0.008). In addition, patients' age, lymphatic and perineurial invasion were associated with the expression of COX-2 (p=0.001, 0.015 and 0.039, respectively). However, other parameters such as stage, tumor size, venous invasion and lymph node metastasis did not show any significant relationship with this marker (all, p>0.05). CONCLUSIONS: COX-2 was expressed in urinary bladder TCC especially in high grade forms, advocating its probable role in the differentiation of this tumor. Accordingly, COX-2 could be a valuable biological target molecule in the evaluation and treatment of patients with bladder TCC.	bladder
Co-regulated expression of TGF-β Variants and miR-21 in bladder cancer.	PURPOSE: To investigate a potential alteration in the expression levels of transforming growth factor β (TGF-β) and miR-21 in bladder cancer tissues. MATERIAL AND METHODS: Using real-time polymerase chain reaction (PCR) method, we examined a potential correlated expression of miR-21 and TGF-β variants in 30 bladder tumors and their marginal/non-tumor biopsy specimens obtained from the same patients. RESULTS: Our data revealed a significant down-regulation of TGF-β variants (P = .03) along with a non-significant alteration in the expression of miR-21 in tumor vs. non-tumor samples. However, in contrast to low-grade tumors, the expression of miR-21 was upregulated in high-grade ones, and the expression level can efficiently discriminate low-grade tumors from high-grade ones (P = .03). CONCLUSION: In accordance to the observed similarity between TGF-β variants and miR-21 gene expression alterations in bladder tumors, treating 5637 bladder cancer cell line with TGF-β recombinant protein caused a significant upregulation of miR-21. The later finding further confirmed a correlated expression of TGF-β and miR-21 in bladder tumors.	bladder
GSTA1, GSTM1, GSTP1, and GSTT1 polymorphisms and susceptibility to smoking-related bladder cancer: a case-control study.	OBJECTIVES: Glutathione S-transferases (GSTs) are a family of enzymes involved in detoxification. Genes encoding for GSTA1, GSTM1, GSTP1, and GSTT1 proteins are polymorphic, which can result in complete or partial loss of enzyme activity. Previous studies have associated polymorphisms of GSTA1, GSTM1, and GSTP1 genes with a higher risk of bladder cancer, but this is still controversial. Potential role of GSTA1 polymorphism in susceptibility to bladder cancer in Whites is lacking. We examined association between GSTA1, GSTM1, GSTP1, and GSTT1 gene variants and bladder cancer risk and evaluated whether they were modified by smoking. MATERIALS AND METHODS: A hospital-based case-control study recruited 201 incidence cases and 122 age-matched controls. Deletion polymorphism of GSTM1 and GSTT1 was identified by polymerase chain reaction method. Single nucleotide polymorphism of GSTA1 and GSTP1 was identified by restriction fragment length polymorphism method. Uniconditional multivariate logistic regression was applied to model association between genetic polymorphisms and bladder cancer risk, as well as effect modification by smoking. RESULTS: No significant difference was observed in the distributions of GSTM1, GSTT1, GSTA1, and GSTP1 gene variants between patients and controls. None of the examined polymorphisms was significantly associated with bladder cancer risk independently. The results of gene-smoking interaction analyses indicated a significant combined effect of smoking and all common GST polymorphisms tested (P for trend = 0.001). However, the most significant effect on bladder cancer risk was observed in smokers carrying lower activity GSTA1-AB/BB and GSTM-null genotype (OR = 3.5, P < 0.05) compared with GSTA1-AA and GSTM1-active non-smokers. Overall, the risk observed did not significantly differ with respect to quantity of cigarettes smoked. However, heavy smokers with GSTM1-null genotype had 2 times higher risk of bladder cancer than GSTM1-null light smokers (OR = 4.8 vs. OR = 2.0) when GSTM1-active non-smokers served as reference group. Smokers carrying both GSTM1-null and GSTA1-AB + BB genotypes exhibited the highest risk of bladder cancer (OR = 2.00, P = 0.123). CONCLUSIONS: Null or low-activity genotypes of the GSTA1, GSTM1, GSTT1, and GSTP1 did not contribute independently towards the risk of bladder cancer in our patients. However, in association with smoking, both low activity GSTA1 and GSTM1-null genotype increase individual susceptibility to bladder cancer.	bladder
Hyperthermia as adjunct to intravesical chemotherapy for bladder cancer.	Nonmuscle invasive bladder cancer remains a very costly cancer to manage because of high recurrence rates requiring long-term surveillance and treatment. Emerging evidence suggests that adjunct and concurrent use of hyperthermia with intravesical chemotherapy after transurethral resection of bladder tumor further reduces recurrence risk and progression to advanced disease. Hyperthermia has both direct and immune-mediated cytotoxic effect on tumor cells including tumor growth arrest and activation of antitumor immune system cells and pathways. Concurrent heat application also acts as a sensitizer to intravesical chemotherapy agents. As such the ability to deliver hyperthermia to the focus of tumor while minimizing damage to surrounding benign tissue is of utmost importance to optimize the benefit of hyperthermia treatment. Existing chemohyperthermia devices that allow for more localized heat delivery continue to pave the way in this effort. Current investigational methods involving heat-activated drug delivery selectively to tumor cells using temperature-sensitive liposomes also offer promising ways to improve chemohyperthermia efficacy in bladder cancer while minimizing toxicity to benign tissue. This will hopefully allow more widespread use of chemohyperthermia to all bladder cancer patients, including metastatic bladder cancer.	bladder